Abilify tolerance

leokitten

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@Hip what I find seriously lacking in that person's post is that they spent
After research (in 10 years of pure desperation you acquire a lot of knowledge ...) I also took 50mg amisulpride, as it uses a complex mechanism to ensure that Abilify does not decrease receptor sensitivity.
but where in the hell is the summary of the research findings and mechanistic explanation??? 10 years of knowledge and haven't shown us any of their work...
 

JES

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It seems to me like pure speculation from the guy. He says 2.5 mg loses its effects because it's dopamine promoting. Meanwhile he says 5 mg works, but that's no wonder since 5 mg is closer to the typical dosage used in (bipolar) depression. Since his problem is depression it might not be of much use for us.

When people with depression attempt antidepressants, they often face the same tolerance issues as people here with Abilify, sometimes over months, sometimes years. The doctor then puts them on a different SSRI and somehow it works again... at least for a while. I don't think anyone studying depression understands why you can work around tolerance by switching to another drug of the same class. He might simply have had more luck with amisulpride, but we don't have him here to tell if it still works for him.
 
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It seems to me like pure speculation from the guy. He says 2.5 mg loses its effects because it's dopamine promoting. Meanwhile he says 5 mg works, but that's no wonder since 5 mg is closer to the typical dosage used in (bipolar) depression. Since his problem is depression it might not be of much use for us.

When people with depression attempt antidepressants, they often face the same tolerance issues as people here with Abilify, sometimes over months, sometimes years. The doctor then puts them on a different SSRI and somehow it works again... at least for a while. I don't think anyone studying depression understands why you can work around tolerance by switching to another drug of the same class. He might simply have had more luck with amisulpride, but we don't have him here to tell if it still works for him.
That’s why I would try for example Cariprazine first
 
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I got an email regarding Abilify Tolerance from Dr. Faltraco from the University of Rostock.
He wrote the following:

“Thank you for your interesting inquiry. We conducted a literature search on the pharmacology of aripriprazole. PThere is no evidence of loss of effectiveness when administered without co-medication. A loss of effectiveness could be linked to a change in pharmacokinetics, so we have focused on this.

However, some substances can alter the drug metabolizing phenotype. For aripiprazole, these are in particular inductors and inhibitors of cytochrome P450 enzyme 2D6. These interactions are added in the Flockhart table.”


I added some photos. You have to focus on the enzyme 2D6! I think there is more to it, but that's all I could get so far.
 

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WantedAlive

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You have to focus on the enzyme 2D6!
Wow, I've just learned a lot more on drug tolerance thanks to this. Thank you @Martin aka paused||M.E.
So reading Wiki explanation on CYP2D6 enzyme, firstly there is considerable variation in the efficiency and amount of this enzyme in individuals, some will be fast metabolizers and some slow. What that means in half life variation between individuals is unknown, but fast metabolizers will need higher dosages to achieve efficacy while slow metabolizers will need lower dosages to avoid toxicity. So a half life of 75 hours could be...what...plus/minus 10%? More?

Then there's the drug interactions you listed as 'inducers' and 'inhibitors'. Drugs that may inhibit CYP2D6 enzyme will slow metabolizing, and inducers will increase metabolizing, either increasing or reducing elimination of the other drug (ie Abilify) respectively. So I see cannabidoil, which I've been taking, is a strong inhibitor of the enzyme which maybe explains why I haven't been able to tolerate higher doses of Abilify. So too, I see, is Doxepin an unspecified inhibitor which I also take. Interestingly, it suggests poor metabolizers will have an exaggerated response to the drug and increased side-effects. So by avoiding these inhibitors, I might reduce the side effects.

So is it just CYP2D6 with Abilify? I'm going to try Abilify again without Doxepin, which I'm currently tapering off, to see if it can help with tolerance, and as well as avoid CBD oil during this trial in a few weeks.
 
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WantedAlive

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So a half life of 75 hours could be...what...plus/minus 10%? More?
Answering my own question here, but it's stated poor CYP2D6 metabolizers can extend aripiprazole half life out to 146 hours! So 3-4 weeks to steady-state. Maybe only up to 8% of the population might fit that criteria, but depending where on the CYP2D6 spectrum we are, between ultrafast and poor-metabolizers, makes a massive difference in tolerance and dosage levels with this drug. Answering my other question, the other enzyme metabolizing aripiprazole is CYP3A4, so influence on this enzyme can also influence efficacy. Reference material here: Aripiprazole Therapy and CYP2D6 Genotype
 
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nryanh94

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Been on for roughly 2 weeks. From day 2 through yesterday it was an insanely positive response, I had almost zero symptoms and it took me out of a bad crash. Today I hit a wall and am pretty exhausted. Am hoping I just over did it (likley) and tolerance has not developed this quickly.
 
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CYP2D6 metabolizes Aripiprazole (Abilify), so changes in CYP2D6 would alter the concentration of Abilify in your blood over time.

For example, someone taking a strong CYP2D6 inhibitor with Abilify could have Abilify plasma concentrations 5 times higher than baseline. Someone with heavily inhibited CYP2D6 who takes 1mg of Abilify might have similar blood concentrations (AUC) as someone else taking as much as 5mg of Abilify.

Other drugs can induce CYP2D6, having the opposite effect of eliminating Abilify from the body faster. This would necessitate higher dosing to compensate.

The Stanford study used doses up to 2mg if I recall correctly. I understand the idea is to leverage some dose-dependent features of Abilify, but I think it would be worth exploring more traditional Abilify doses for anyone who previously responded to low doses. A proper trial of Abilify up to a more standard dose (preferably under the supervision of a doctor) might be worthwhile.
 
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CYP2D6 metabolizes Aripiprazole (Abilify), so changes in CYP2D6 would alter the concentration of Abilify in your blood over time.

For example, someone taking a strong CYP2D6 inhibitor with Abilify could have Abilify plasma concentrations 5 times higher than baseline. Someone with heavily inhibited CYP2D6 who takes 1mg of Abilify might have similar blood concentrations (AUC) as someone else taking as much as 5mg of Abilify.

Other drugs can induce CYP2D6, having the opposite effect of eliminating Abilify from the body faster. This would necessitate higher dosing to compensate.

The Stanford study used doses up to 2mg if I recall correctly. I understand the idea is to leverage some dose-dependent features of Abilify, but I think it would be worth exploring more traditional Abilify doses for anyone who previously responded to low doses. A proper trial of Abilify up to a more standard dose (preferably under the supervision of a doctor) might be worthwhile.
My father talked to a doc (ME doc) who uses up to 10mg with success.
 
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Does anyone know for certain if LDN (naltrexone) in a low dose inhibits CYP2D6? It seems Ron checked (Janet mentioned he ran some tests on LDN and the CYP2D6 enzyme) and turns out it does not inhibit the enzyme to any significant degree (at doses of say 4.5mg).